Bone material dispensing apparatus and methods

ABSTRACT

A bone material dispensing apparatus for preparing, mixing, and dispensing bone material into a foldable container is provided. In some embodiments, the dispensing apparatus comprises a tray and a foldable container. The tray includes a mixing surface, a dispensing surface and a means to measure the amount of material to be dispensed. A kit including a tray, a foldable container, and a spatula are also provided. A method of using the dispensing apparatus to deliver the bone material to a bone defect is also provided.

BACKGROUND

Mammalian bone tissue contains one or more proteinaceous materials,presumably active during growth and natural bone healing that can inducea developmental cascade of cellular events resulting in bone formation.Various developmental factors are present in bone. These include bonemorphogenetic proteins (BMPs), bone inductive proteins, bone growthfactors, osteogenic proteins, or osteoinductive proteins. While theseproteins have different effects and functions, these proteins will bereferred to collectively herein as osteoinductive factors.

These osteoinductive factors are present within the compound structureof cortical bone and are present at very low concentrations, forexample, 0.003% by weight. Osteoinductive factors direct thedifferentiation of pluripotent mesenchymal cells into osteoprogenitorcells that form osteoblasts. Proper demineralization of cortical boneexposes these osteoinductive factors in bone rendering itosteoinductive.

The rapid and effective repair of bone defects caused by injury,disease, wounds, or surgery has long been a goal of orthopedic surgery.Toward this end, a number of materials have been used or proposed foruse in the repair of bone defects. The biological, physical, andmechanical properties of the materials are among the major factorsinfluencing their suitability and performance in various orthopedicapplications.

Autologous cancellous bone (ACB) has long been considered the goldstandard for bone grafts. ACB includes osteogenic cells, which have thepotential to assist in bone healing, is nonimmunogenic, and hasstructural and functional characteristics that are appropriate for ahealthy recipient. Some people do not have adequate amounts of ACB forharvesting. These people include, for example, older people and peoplewho have had previous surgeries. A majority of people, however, do haveadequate amounts of ACB for harvesting. There may nevertheless bereluctance to harvest ACB because of pain at the harvest site andpotential donor site morbidity.

Conventionally, bone tissue regeneration is achieved by filling a bonedefect with a bone material, for example, a bone graft. Over time, thebone graft is incorporated by the host and new bone remodels the bonegraft. Bone material can include bone from the patient's own body orartificial, synthetic, or natural substitute bone material.

Demineralized bone matrix (DBM) is bone material commonly used inorthopedic procedures to substitute for, or extend the volume of, anautograft or allograft bone. Demineralized bone matrix is typicallyderived from cadavers. The bone is removed aseptically and/or treated tokill any infectious agents. The bone is then particulated by milling orgrinding and then the mineral components are extracted, for example, bysoaking the bone in an acidic solution.

To deliver the bone material to the bone defect, often times the bonematerial is mixed with liquid or a therapeutic agent, powder, fiber orgranular material. Mixing devices that are currently available arecumbersome to use and do not allow uniform and easy mixing of material.Further, transfer of bone material to the delivery device is often doneby crude packing of the bone delivery device and there is unwantedspillage of bone material out of the device, which may increase the riskof contamination of the bone material. Currently available deliverydevices often lack precision in measuring the bone material for deliveryto the target bone defect.

It would therefore be desirable to provide a bone material dispensingapparatus that allows easy and precise measuring and mixing of bonematerial. Further, a bone material dispensing apparatus that allowseasier loading of the delivery device, which reduces the risk ofcontamination and spillage of bone material from the delivery devicewould also be desirable.

SUMMARY

In some embodiments, there is a bone material dispensing apparatus thatallows easy precision measuring and mixing of bone material. The bonematerial dispensing apparatus allows easier loading of the deliverydevice, which reduces the risk of contamination and spillage of bonematerial. In some embodiments, the bone material dispensing apparatusallows uniform mixing and measuring of the bone material, reducingclogging and friction resistance in the bone material dispensingapparatus.

In some embodiments, there is a bone material dispensing apparatus,comprising: a tray having a proximal end, a distal end, and a bonematerial dispensing surface disposed between the proximal end and thedistal end of the tray; a foldable container configured to removablyengage the proximal end of the tray, the foldable container beingmovable in a folded configuration and an unfolded configuration about afold line in the foldable container, the foldable container having anupper compartment and a lower compartment, the lower compartment of thefoldable container configured to receive a bone material from thedispensing surface of the tray when the foldable container removablyengages the proximal end of the tray in the unfolded configuration andwhen the foldable container is in the folded configuration, the uppercompartment is configured to enclose the bone material in the lowercompartment.

In some embodiments, there is a kit for dispensing bone material, thekit comprising: a tray having a proximal end, a distal end, and a bonematerial dispensing surface disposed between the proximal end and thedistal end of the tray, the dispensing surface comprising a plurality ofridges extending from the distal end of the tray to a region adjacent tothe proximal end of the tray, each of the plurality of ridges having aside wall and each of the plurality of ridges spaced a distance apartfrom each other such that a measured amount of a bone material can beplaced between each side wall of at least two of the plurality of ridgesfor measured dispensing of the bone material; a foldable containerconfigured to removably engage the proximal end of the tray, thefoldable container being movable in a folded configuration and anunfolded configuration about a fold line in the foldable container, thefoldable container having an upper compartment and a lower compartment,the lower compartment of the foldable container configured to receivebone material from the dispensing surface of the tray when the foldablecontainer removably engages the proximal end of the tray in the unfoldedconfiguration and when the foldable container is in the foldedconfiguration, the upper compartment is configured to enclose the bonematerial in the lower compartment, wherein the proximal end of the traycomprises a first channel and a second channel configured to hold theupper compartment and the lower compartment of the foldable container,the first channel of the proximal end of the tray dimensioned tocorrespond to the upper compartment of the foldable container and thesecond channel of the proximal end of the tray dimensioned to correspondto the lower compartment of the foldable container such that at least inthe unfolded configuration, the foldable container is held by the tray;and a spatula configured to dispense bone material from the dispensingsurface into the foldable container.

In some embodiments, there is a method of filling bone material into afoldable container, the method comprising: placing a bone material in oron a dispensing surface of a tray, the tray having a proximal end, adistal end, and the dispensing surface disposed between the proximal endand the distal end of the tray; transferring the bone material from thedispensing surface of the tray to fill a foldable container with thebone material, the foldable container configured to removably engage theproximal end of the tray, the foldable container being movable in afolded configuration and an unfolded configuration about a fold line inthe foldable container, the foldable container having an uppercompartment and a lower compartment, the lower compartment of thefoldable container configured to receive the bone material from thedispensing surface of the tray when the foldable container removablyengages the proximal end of the tray in the unfolded configuration; andfolding the upper compartment on the lower compartment of the foldablecontainer to enclose the bone material in the foldable container whenthe foldable container is in the folded configuration thereby fillingthe foldable container with bone material.

While multiple embodiments are disclosed, still other embodiments of thepresent disclosure will become apparent to those skilled in the art fromthe following detailed description. As will be apparent, the disclosureis capable of modifications in various obvious aspects, all withoutdeparting from the spirit and scope of the present disclosure.Accordingly, the detailed description is to be regarded as illustrativein nature and not restrictive.

BRIEF DESCRIPTION OF THE FIGURES

In part, other aspects, features, benefits and advantages of theembodiments will be apparent with regard to the following description,appended claims and accompanying figures where:

FIG. 1 depicts a perspective view of a bone material dispensingapparatus according to an aspect of the present application, where thefoldable container is in a folded configuration and the tray containssome bone material;

FIG. 2 depicts a perspective view of a bone material dispensingapparatus of FIG. 1 where the foldable container is in an unfoldedconfiguration and the foldable container is loaded with some bonematerial;

FIG. 3 depicts a perspective view of a bone material dispensingapparatus according to another aspect of the present application wherethe foldable container is in a folded configuration and the foldablecontainer partially encloses bone material;

FIG. 4 depicts a perspective view of a bone material dispensingapparatus according to another aspect of the present application wherethe tray has ridges for measured dispensing of bone material;

FIG. 5 depicts a perspective view of a bone material dispensingapparatus according to another aspect of the present application wherethe foldable container is in an unfolded configuration and the foldablecontainer is loaded with some bone material;

FIG. 6 depicts a perspective view of a bone material dispensingapparatus according to another aspect of the present application wherethe foldable container is in a folded configuration and the foldablecontainer is loaded with bone material;

FIG. 7 depicts a perspective view of a foldable container according toan aspect of the present application where the foldable container is inan unfolded configuration and a folded configuration, and the foldablecontainer has slots and tabs for locking the foldable container in thefolded configuration;

FIG. 8 depicts a perspective view of a foldable container with aninsertion device according to an aspect of the present application;

FIG. 9 depicts a perspective view of a foldable container with a sleevefor the container according to an aspect of the present application;

FIG. 10 depicts a perspective view of a foldable container with a sleevefor the container according to another aspect of the presentapplication;

FIG. 11 depicts a perspective view of a bone material dispensingapparatus according to another aspect of the present application, whichincludes a spatula, foldable container, plunger, needle and needlecover;

FIG. 12 depicts variously shaped tips that a foldable container cancomprise according to an aspect of the present application; and

FIG. 13 depicts a perspective view of spatulas according to anotheraspect of the present application.

FIG. 14 depicts a perspective view of another embodiment of the foldablecontainer in the open and closed configuration according to anotheraspect of the present application.

It is to be understood that the figures are not drawn to scale. Further,the relation between objects in a figure may not be to scale, and may infact have a reverse relationship as to size. The figures are intended tobring understanding and clarity to the structure of each object shown,and thus, some features may be exaggerated in order to illustrate aspecific feature of a structure.

DETAILED DESCRIPTION Definitions

It is noted that, as used in this specification and the appended claims,the singular forms “a,” “an,” and “the,” include plural referents unlessexpressly and unequivocally limited to one referent. For example,reference to “a container” includes one, two, three or more containers.

The term “allograft” refers to a graft of tissue obtained from a donorof the same species as, but with a different genetic make-up from, therecipient, as a tissue transplant between two humans.

The term “autologous” refers to being derived or transferred from thesame individual's body, such as for example an autologous bone marrowtransplant.

The term “xenograft” refers to tissue or organs from an individual ofone species transplanted into or grafted onto an organism of anotherspecies, genus, or family.

The term “mammal” refers to organisms from the taxonomy class“mammalian,” including, but not limited to, humans; other primates, suchas chimpanzees, apes, orangutans and monkeys; rats, mice, cats, dogs,cows, horses, etc.

The term “patient” refers to a biological system to which a treatmentcan be administered. A biological system can include, for example, anindividual cell, a set of cells (e.g., a cell culture), an organ, or atissue. Additionally, the term “patient” can refer to animals,including, without limitation, humans.

The term “bone material” includes natural and/or inorganic material suchas, for example, inorganic ceramic and/or bone substitute material. Thebone material can also include natural bone material such as, forexample, bone which is cortical, cancellous or cortico-cancellous ofautogenous, allogenic, xenogenic, or transgenic origin. In someembodiments, bone material can include demineralized bone material suchas, for example, substantially demineralized bone material, partiallydemineralized bone material, or fully demineralized bone material.

“Demineralized” as used herein, refers to any material generated byremoving mineral material from tissue, e.g., bone tissue. In certainembodiments, the demineralized compositions described herein includepreparations containing less than 5% calcium and preferably less than 1%calcium by weight. Partially demineralized bone (e.g., preparations withgreater than 5% calcium by weight but containing less than 100% of theoriginal starting amount of calcium) is also considered within the scopeof the application. In some embodiments, demineralized bone has lessthan 95% of its original mineral content.

In some embodiments, demineralized bone has less than 95% of itsoriginal mineral content. In some embodiments, demineralized bone hasless than 95, 94, 93, 92, 91, 90, 89, 88, 87, 86, 85, 84, 83, 82, 81,80, 79, 78, 77, 76, 75, 74, 73, 72, 71, 70, 69, 68, 67, 66, 65, 64, 63,62, 61, 60, 59, 58, 57, 56, 55, 54, 53, 52, 51, 50, 49, 48, 47, 46, 45,44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27,26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9,8, 7, 6 and/or 5% of its original content. In some embodiments,“demineralized” is intended to encompass such expressions as“substantially demineralized,” “superficially demineralized,” “partiallydemineralized,” “surface demineralized,” and “fully demineralized.”

“Partially demineralized” is intended to encompass “surfacedemineralized.” “Partially demineralized bone” is intended to refer topreparations with greater than 5% calcium by weight but containing lessthan 100% of the original starting amount of calcium. In someembodiments, partially demineralized comprises 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 and/or 99% ofthe original starting amount of calcium.

In some embodiments, the demineralized bone may be surface demineralizedfrom about 1-99%. In some embodiments, the demineralized bone is 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76,77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94,95, 96, 97, 98 and/or 99% surface demineralized. In various embodiments,the demineralized bone may be surface demineralized from about 15-25%.In some embodiments, the demineralized bone is 15, 16, 17, 18, 19, 20,21, 22, 23, 24 and/or 25% surface demineralized.

“Superficially demineralized” as used herein, refers to bone-derivedelements possessing at least about 90 weight percent of their originalinorganic mineral content, the expression “partially demineralized” asused herein refers to bone-derived elements possessing from about 8 toabout 90 weight percent of their original inorganic mineral content andthe expression “fully demineralized” as used herein refers to bonecontaining less than 8% of its original mineral context.

“Demineralized bone matrix” as used herein, refers to any materialgenerated by removing mineral material from bone tissue. In preferredembodiments, the DBM compositions as used herein include preparationscontaining less than 5% calcium and preferably less than 1% calcium byweight.

“Biocompatible” as used herein, refers to materials that, uponadministration in vivo, do not induce undesirable long-term effects.

“Osteoconductive” as used herein, refers to the ability of anon-osteoinductive substance to serve as a suitable template orsubstance along which bone may grow.

“Osteogenic”, as used herein, refers to the ability of an agent,material, or implant to enhance or accelerate the growth of new bonetissue by one or more mechanisms such as osteogenesis, osteoconduction,and/or osteoinduction.

“Osteoinductive” as used herein, refers to the quality of being able torecruit cells from the host that have the potential to stimulate newbone formation. Any material that can induce the formation of ectopicbone in the soft tissue of an animal is considered osteoinductive. Forexample, most osteoinductive materials induce bone formation in athymicrats when assayed according to the method of Edwards et al.,“Osteoinduction of Human Demineralized Bone: Characterization in a RatModel,” Clinical Orthopaedics & Rel. Res., 357:219-228, December 1998,incorporated herein by reference.

The terms “upper”, “lower”, “top”, “bottom”, “side”, “proximal”,“distal” and so forth have been used herein merely for convenience todescribe the present invention and its parts as oriented in thedrawings. It is to be understood, however, that these terms are in noway limiting to the disclosure since the delivery systems describedherein may obviously be disposed in different orientations when in use.

The term “removably engage” includes engagement of two or morecomponents that can be used or combined into one element via theengagement of the two or more elements with a connecting means, alocking means, or by placing the elements tightly together. The two ormore elements may be positioned adjacent to each other and each includea contacting surface. For example, a foldable container may be placedadjacent to the proximal end of the tray such that the foldablecontainer removably engages the tray. In some embodiments, the foldablecontainer may snap fit into the proximal end of the tray such that thefoldable container removably engages the tray.

For the purposes of this specification and appended claims, unlessotherwise indicated, all numbers expressing quantities of ingredients,percentages or proportions of materials, reaction conditions, and othernumerical values used in the specification and claims, are to beunderstood as being modified in all instances by the term “about.”Accordingly, unless indicated to the contrary, the numerical parametersset forth in the following specification and attached claims areapproximations that may vary depending upon the desired propertiessought to be obtained by the present invention. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical parameter shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques.

Notwithstanding the numerical ranges and parameters set forth herein,the broad scope of the invention is an approximation, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Moreover, all ranges disclosed hereinare to be understood to encompass any and all subranges subsumedtherein. For example, a range of “1 to 10” includes any and allsubranges between (and including) the minimum value of 1 and the maximumvalue of 10, that is, any and all subranges having a minimum value ofequal to or greater than 1 and a maximum value of equal to or less than10, e.g., 5.5 to 10.

Reference will now be made in detail to certain embodiments of thedisclosure, examples of which are illustrated in the accompanyingfigures. While the disclosure will be described in conjunction with theillustrated embodiments, it will be understood that they are notintended to limit the disclosure to those embodiments. On the contrary,the disclosure is intended to cover all alternatives, modifications, andequivalents that may be included within the disclosure as defined by theappended claims.

The headings below are not meant to limit the disclosure in any way;embodiments under any one heading may be used in conjunction withembodiments under any other heading.

Bone Material

In some embodiments, there is a bone material dispensing apparatus thatallows easy precision measuring and mixing of bone material. The bonematerial dispensing apparatus allows easier loading of the deliverydevice, which reduces the risk of contamination and spillage of bonematerial. In some embodiments, the bone material dispensing apparatusallows uniform mixing and measuring of the bone material, reducingclogging and friction resistance in the bone material dispensingapparatus. The bone material can be in granular, paste, putty or powderforms.

In some embodiments, the bone material can be demineralized bonematerial. The demineralized bone material can comprise demineralizedbone, powder, chips, granules, shards, fibers or other shapes havingirregular or random geometries. These can include, for example,substantially demineralized, partially demineralized, or fullydemineralized cortical and cancellous bone. These also include surfacedemineralization, where the surface of the bone construct issubstantially demineralized, partially demineralized, or fullydemineralized, yet the body of the bone construct is fully mineralized.The configuration of the bone material can be obtained by milling,shaving, cutting or machining whole bone as described in, for example,U.S. Pat. No. 5,899,939. The entire disclosure is herein incorporated byreference into the present disclosure.

In some embodiments, the bone material can comprise elongateddemineralized bone fibers having an average length to average thicknessratio or aspect ratio of the fibers from about 50:1 to about 1000:1. Inoverall appearance the elongated demineralized bone fibers can be round,spherical, granular, elongated, powders, chips, fibers, cylinders,threads, narrow strips, thin sheets, or a combination thereof. In someembodiments, the bone material comprises elongated demineralized bonefibers and chips. In some embodiments, the bone material comprises fullydemineralized fibers and surface demineralized chips. In someembodiments, the ratio of fibers to chips or powders is from about 5,10, 15, 20, 25, 30, 35, 40, or 45 fibers to about 30, 35, 40, 45, 50,55, 60, 65, or 70 chips.

In some embodiments, the bone material comprises demineralized bonematrix fibers and demineralized bone matrix chips in a 30:60 ratio. Insome embodiments, the bone material comprises demineralized bone matrixfibers and demineralized bone matrix chips in a ratio of 25:75 to about75:25 fibers to chips.

In some embodiments, the bone material can be an inorganic material,such as an inorganic ceramic and/or bone substitute material. Exemplaryinorganic materials or bone substitute materials include but are notlimited to aragonite, dahlite, calcite, brushite, amorphous calciumcarbonate, vaterite, weddellite, whewellite, struvite, urate,ferrihydrate, francolite, monohydrocalcite, magnetite, goethite, dentin,calcium carbonate, calcium sulfate, calcium phosphosilicate, sodiumphosphate, calcium aluminate, calcium phosphate, hydroxyapatite,alpha-tricalcium phosphate, dicalcium phosphate, β-tricalcium phosphate,tetracalcium phosphate, amorphous calcium phosphate, octacalciumphosphate, BIOGLASS™ fluoroapatite, chlorapatite, magnesium-substitutedtricalcium phosphate, carbonate hydroxyapatite, substituted forms ofhydroxyapatite (e.g., hydroxyapatite derived from bone may besubstituted with other ions such as fluoride, chloride, magnesiumsodium, potassium, etc.), or combinations or derivatives thereof.

In some embodiments, the bone material can comprise mineral particles,which comprise tricalcium phosphate and hydroxyapatite in a ratio ofabout 80:20 to about 90:10. In some embodiments, the mineral particlescan comprise tricalcium phosphate and hydroxyapatite in a ratio of about70:30 to about 95:5. In some embodiments, the mineral particles cancomprise tricalcium phosphate and hydroxyapatite in a ratio of about85:15.

In some embodiments, the bone material may be seeded with harvested bonecells and/or bone tissue, such as for example, cortical bone, autogenousbone, allogenic bones and/or xenogeneic bone while it is mixed.

In some embodiments, the bone material may be mixed with one or moretherapeutic agents, for example, an anti-inflammatory agent, ananalgesic agent, an osteoinductive growth factor, an antimicrobial agentor a combination thereof. Osteoinductive agents include one or moremembers of the family of Bone Morphogenetic Proteins (“BMPs”). BMPs area class of proteins thought to have osteoinductive or growth-promotingactivities on endogenous bone tissue, or function as pro-collagenprecursors. Known members of the BMP family include, but are not limitedto, BMP-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9,BMP-10, BMP-11, BMP-12, BMP-13, BMP-14 (GDF-5), BMP-15, BMP-16, BMP-17,BMP-18 as well as polynucleotides or polypeptides thereof, as well asmature polypeptides or polynucleotides encoding the same.

BMPs utilized as osteoinductive agents comprise one or more of BMP-1;BMP-2; BMP-3; BMP-4; BMP-5; BMP-6; BMP-7; BMP-8; BMP-9; BMP-10; BMP-11;BMP-12; BMP-13; BMP-15; BMP-16; BMP-17; or BMP-18; as well as anycombination of one or more of these BMPs, including full length BMPs orfragments thereof, or combinations thereof, either as polypeptides orpolynucleotides encoding the polypeptide fragments of all of the recitedBMPs. The isolated BMP osteoinductive agents may be administered aspolynucleotides, polypeptides, full length protein or combinationsthereof.

Indeed, the osteoinductive factors are the recombinant human bonemorphogenetic proteins (rhBMPs) because they are available in unlimitedsupply and do not transmit infectious diseases. In some embodiments, thebone morphogenetic protein is a rhBMP-2, rhBMP-4, rhBMP-7, orheterodimers thereof. Recombinant BMP-2 can be used at a concentrationof about 0.4 mg/mL to about 10.0 mg/mL, preferably about 1.5 mg/mL.

The bone material may include or be mixed with one or more members fromthe TGF-β superfamily. For example, the matrix may include AMH, ARTN,GDF1, GDF10, GDF11, GDF15, GDF2, GDF3, GDF3A, GDF5, GDF6, GDF7, GDF8,GDF9, GDNF, INHA, INHBA, INHBB, INHBC, INHBE, LEFTY1, LEFTY2, MSTN,NODAL, NRTN, PSPN, TGFB1, TGFB2, TGFB3, FGF, basic FGF, VEGF,insulin-like growth factor, EGF, PDGF, nerve growth factor orcombinations thereof.

The bone material may include or be mixed with a therapeutic agentincluding, but not limited to, IL-1 inhibitors, such Kineret®(anakinra), which is a recombinant, non-glycosylated form of the humaninterleukin-1 receptor antagonist (IL-1Ra), or AMG 108, which is amonoclonal antibody that blocks the action of IL-1. The bone materialmay include or be mixed with therapeutic agents including excitatoryamino acids such as glutamate and aspartate, antagonists or inhibitorsof glutamate binding to NMDA receptors, AMPA receptors, and/or kainatereceptors. The bone material may include or be mixed with therapeuticagents to reduce inflammation including but not limited to interleukin-1receptor antagonists, thalidomide (a TNF-α release inhibitor),thalidomide analogues (which reduce TNF-α production by macrophages),quinapril (an inhibitor of angiotensin II, which upregulates TNF-α),interferons such as IL-11 (which modulate TNF-α receptor expression), oraurin-tricarboxylic acid (which inhibits TNF-α).

The bone material may include or be mixed with a therapeutic agentincluding, but not limited to, an analgesic agent. Examples of analgesicagents include, but are not limited to, acetaminophen, tramadol,lidocaine, bupivacaine, ropivacaine, opioid analgesics such asbuprenorphine, butorphanol, dextromoramide, dezocine,dextropropoxyphene, diamorphine, fentanyl, alfentanil, sufentanil,hydrocodone, hydromorphone, ketobemidone, levomethadyl, levorphanol,meperidine, methadone, morphine, nalbuphine, opium, oxycodone,papaveretum, pentazocine, pethidine, phenoperidine, piritramide,dextropropoxyphene, remifentanil, sufentanil, tilidine, tramadol,codeine, dihydrocodeine, meptazinol, dezocine, eptazocine, flupirtine ora combination thereof.

The bone material may include or be mixed with a therapeutic agentincluding, but not limited to, an anti-inflammatory agent. An example ofan anti-inflammatory agent includes, but is not limited to, clonidine,sulindac, sulfasalazine, naroxyn, diclofenac, indomethacin, ibuprofen,flurbiprofen, ketoprofen, aclofenac, aloxiprin, aproxen, aspirin,diflunisal, fenoprofen, mefenamic acid, naproxen, phenylbutazone,piroxicam, meloxicam, salicylamide, salicylic acid, desoxysulindac,tenoxicam, ketoralac, clonidine, flufenisal, salsalate, triethanolaminesalicylate, aminopyrine, antipyrine, oxyphenbutazone, apazone,cintazone, flufenamic acid, clonixeril, clonixin, meclofenamic acid,flunixin, colchicine, demecolcine, allopurinol, oxypurinol, benzydaminehydrochloride, dimefadane, indoxole, intrazole, mimbane hydrochloride,paranylene hydrochloride, tetrydamine, benzindopyrine hydrochloride,fluprofen, ibufenac, naproxol, fenbufen, cinchophen, diflumidone sodium,fenamole, flutiazin, metazamide, letimide hydrochloride, nexeridinehydrochloride, octazamide, molinazole, neocinchophen, nimazole,proxazole citrate, tesicam, tesimide, tolmetin, triflumidate, fenamates(mefenamic acid, meclofenamic acid), nabumetone, celecoxib, etodolac,nimesulide, apazone, gold, tepoxalin; dithiocarbamate, or a combinationthereof.

Anti-inflammatory agents also include steroids, such as for example,21-acetoxypregnenolone, alclometasone, algestone, amcinonide,beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol,clobetasone, clocortolone, cloprednol, corticosterone, cortisone,cortivazol, deflazacort, desonide, desoximetasone, dexamethasone,dexamethasone 21-acetate, dexamethasone 21-phosphate di-Na salt,diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort,flucloronide, flumethasone, flunisolide, fluocinolone acetonide,fluocinonide, fluocortin butyl, fluocortolone, fluorometholone,fluperolone acetate, fluprednidene acetate, fluprednisolone,flurandrenolide, fluticasone propionate, formocortal, halcinonide,halobetasol propionate, halometasone, halopredone acetate,hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone,medrysone, meprednisone, methylprednisolone, mometasone furoate,paramethasone, prednicarbate, prednisolone, prednisolone25-diethylamino-acetate, prednisolone sodium phosphate, prednisone,prednival, prednylidene, rimexolone, tixocortol, triamcinolone,triamcinolone acetonide, triamcinolone benetonide, triamcinolonehexacetonide or a combination thereof.

The bone material may include or be mixed with a therapeutic agentincluding, but not limited to, a statin. Examples of a useful statininclude, but are not limited to, atorvastatin, simvastatin, pravastatin,cerivastatin, mevastatin (see U.S. Pat. No. 3,883,140, the entiredisclosure is herein incorporated by reference), velostatin (also calledsynvinolin; see U.S. Pat. Nos. 4,448,784 and 4,450,171 these entiredisclosures are herein incorporated by reference), fluvastatin,lovastatin, rosuvastatin and fluindostatin (Sandoz XU-62-320),dalvastain (EP Appln. Publn. No. 738510 A2, the entire disclosure isherein incorporated by reference), eptastatin, pitavastatin, orpharmaceutically acceptable salts thereof or a combination thereof. Invarious embodiments, the statin may comprise mixtures of (+)R and (−)-Senantiomers of the statin. In various embodiments, the statin maycomprise a 1:1 racemic mixture of the statin.

In some embodiments, the bone material can include an antimicrobialagent. In some embodiments, the antimicrobial agent can include one ormore of triclosan, also known as 2,4,4′-trichloro-2′-hydroxydiphenylether, chlorhexidine and its salts, including chlorhexidine acetate,chlorhexidine gluconate, chlorhexidine hydrochloride, and chlorhexidinesulfate, silver and its salts, including silver acetate, silverbenzoate, silver carbonate, silver citrate, silver iodate, silveriodide, silver lactate, silver laurate, silver nitrate, silver oxide,silver palmitate, silver protein, and silver sulfadiazine, polymyxin,tetracycline, aminoglycosides, such as tobramycin and gentamicin,rifampicin, bacitracin, neomycin, chloramphenicol, miconazole,quinolones such as oxolinic acid, norfloxacin, nalidixic acid,pefloxacin, enoxacin and ciprofloxacin, penicillins such as oxacillinand pipracil, nonoxynol 9, fusidic acid, cephalosporins, or combinationsthereof.

Examples of antimicrobial agents include, by way of illustration and notlimited to, acedapsone; acetosulfone sodium; alamecin; alexidine;amdinocillin; amdinocillin pivoxil; amicycline; amifloxacin; amifloxacinmesylate; amikacin; amikacin sulfate; aminosalicylic acid;aminosalicylate sodium; amoxicillin; amphomycin; ampicillin; ampicillinsodium; apalcillin sodium; apramycin; aspartocin; astromicin sulfate;avilamycin; avoparcin; azithromycin; azlocillin; azlocillin sodium;bacampicillin hydrochloride; bacitracin; bacitracin methylenedisalicylate; bacitracin zinc; bambermycins; benzoylpas calcium;berythromycin; betamicin sulfate; biapenem; biniramycin; biphenaminehydrochloride; bispyrithione magsulfex; butikacin; butirosin sulfate;capreomycin sulfate; carbadox; carbenicillin disodium; carbenicillinindanyl sodium; carbenicillin phenyl sodium; carbenicillin potassium;carumonam sodium; cefaclor; cefadroxil; cefamandole; cefamandole nafate;cefamandole sodium; cefaparole; cefatrizine; cefazaflur sodium;cefazolin; cefazolin sodium; cefbuperazone; cefdinir; cefepime; cefepimehydrochloride; cefetecol; cefixime; cefmenoxime hydrochloride;cefmetazole; cefmetazole sodium; cefonicid monosodium; cefonicid sodium;cefoperazone sodium; ceforanide; cefotaxime sodium; cefotetan; cefotetandisodium; cefotiam hydrochloride; cefoxitin; cefoxitin sodium;cefpimizole; cefpimizole sodium; cefpiramide; cefpiramide sodium;cefpirome sulfate; cefpodoxime proxetil; cefprozil; cefroxadine;cefsulodin sodium; ceftazidime; ceftibuten; ceftizoxime sodium;ceftriaxone sodium; cefuroxime; cefuroxime axetil; cefuroxime pivoxetil;cefuroxime sodium; cephacetrile sodium; cephalexin; cephalexinhydrochloride; cephaloglycin; cephaloridine; cephalothin sodium;cephapirin sodium; cephradine; cetocycline hydrochloride; cetophenicol;chloramphenicol; chloramphenicol palmitate; chloramphenicol pantothenatecomplex; chloramphenicol sodium succinate; chlorhexidine phosphanilate;chloroxylenol; chlortetracycline bisulfate; chlortetracyclinehydrochloride; cinoxacin; ciprofloxacin; ciprofloxacin hydrochloride;cirolemycin; clarithromycin; clinafloxacin hydrochloride; clindamycin;clindamycin hydrochloride; clindamycin palmitate hydrochloride;clindamycin phosphate; clofazimine; cloxacillin benzathine; cloxacillinsodium; chlorhexidine, cloxyquin; colistimethate sodium; colistinsulfate; coumermycin; coumermycin sodium; cyclacillin; cycloserine;dalfopristin; dapsone; daptomycin; demeclocycline; demeclocyclinehydrochloride; demecycline; denofungin; diaveridine; dicloxacillin;dicloxacillin sodium; dihydrostreptomycin sulfate; dipyrithione;dirithromycin; doxycycline; doxycycline calcium; doxycycline fosfatex;doxycycline hyclate; droxacin sodium; enoxacin; epicillin;epitetracycline hydrochloride; erythromycin; erythromycin acistrate;erythromycin estolate; erythromycin ethylsuccinate; erythromycingluceptate; erythromycin lactobionate; erythromycin propionate;erythromycin stearate; ethambutol hydrochloride; ethionamide;fleroxacin; floxacillin; fludalanine; flumequine; fosfomycin; fosfomycintromethamine; fumoxicillin; furazolium chloride; furazolium tartrate;fusidate sodium; fusidic acid; ganciclovir and ganciclovir sodium;gentamicin sulfate; gloximonam; gramicidin; haloprogin; hetacillin;hetacillin potassium; hexedine; ibafloxacin; imipenem; isoconazole;isepamicin; isoniazid; josamycin; kanamycin sulfate; kitasamycin;levofuraltadone; levopropylcillin potassium; lexithromycin; lincomycin;lincomycin hydrochloride; lomefloxacin; lomefloxacin hydrochloride;lomefloxacin mesylate; loracarbef; mafenide; meclocycline; meclocyclinesulfosalicylate; megalomicin potassium phosphate; mequidox; meropenem;methacycline; methacycline hydrochloride; methenamine; methenaminehippurate; methenamine mandelate; methicillin sodium; metioprim;metronidazole hydrochloride; metronidazole phosphate; mezlocillin;mezlocillin sodium; minocycline; minocycline hydrochloride; mirincamycinhydrochloride; monensin; monensin sodiumr; nafcillin sodium; nalidixatesodium; nalidixic acid; natainycin; nebramycin; neomycin palmitate;neomycin sulfate; neomycin undecylenate; netilmicin sulfate;neutramycin; nifuiradene; nifuraldezone; nifuratel; nifuratrone;nifurdazil; nifurimide; nifiupirinol; nifurquinazol; nifurthiazole;nitrocycline; nitrofurantoin; nitromide; norfloxacin; novobiocin sodium;ofloxacin; onnetoprim; oxacillin and oxacillin sodium; oximonam;oximonam sodium; oxolinic acid; oxytetracycline; oxytetracyclinecalcium; oxytetracycline hydrochloride; paldimycin; parachlorophenol;paulomycin; pefloxacin; pefloxacin mesylate; penamecillin; penicillinssuch as penicillin g benzathine, penicillin g potassium, penicillin gprocaine, penicillin g sodium, penicillin v, penicillin v benzathine,penicillin v hydrabamine, and penicillin v potassium; pentizidonesodium; phenyl aminosalicylate; piperacillin sodium; pirbenicillinsodium; piridicillin sodium; pirlimycin hydrochloride; pivampicillinhydrochloride; pivampicillin pamoate; pivampicillin probenate; polymyxinb sulfate; porfiromycin; propikacin; pyrazinamide; pyrithione zinc;quindecamine acetate; quinupristin; racephenicol; ramoplanin; ranimycin;relomycin; repromicin; rifabutin; rifametane; rifamexil; rifamide;rifampin; rifapentine; rifaximin; rolitetracycline; rolitetracyclinenitrate; rosaramicin; rosaramicin butyrate; rosaramicin propionate;rosaramicin sodium phosphate; rosaramicin stearate; rosoxacin;roxarsone; roxithromycin; sancycline; sanfetrinem sodium; sarmoxicillin;sarpicillin; scopafungin; sisomicin; sisomicin sulfate; sparfloxacin;spectinomycin hydrochloride; spiramycin; stallimycin hydrochloride;steffimycin; streptomycin sulfate; streptonicozid; sulfabenz,sulfabenzamide; sulfacetamide; sulfacetamide sodium; sulfacytine;sulfadiazine; sulfadiazine sodium; sulfadoxine; sulfalene;sulfamerazine; sulfameter; sulfamethazine; sulfamethizole;sulfamethoxazole; sulfamonomethoxine; sulfamoxole; sulfanilate zinc;sulfanitran; sulfasalazine; sulfasomizole; sulfathiazole; sulfazamet;sulfisoxazole; sulfisoxazole acetyl; sulfisboxazole diolamine;sulfomyxin; sulopenem; sultamricillin; suncillin sodium; talampicillinhydrochloride; teicoplanin; temafloxacin hydrochloride; temocillin;tetracycline; tetracycline hydrochloride; tetracycline phosphatecomplex; tetroxoprim; thiamphenicol; thiphencillin potassium;ticarcillin cresyl sodium; ticarcillin disodium; ticarcillin monosodium;ticlatone; tiodonium chloride; tobramycin; tobramycin sulfate;tosufloxacin; trimethoprim; trimethoprim sulfate; trisulfapyrimidines;troleandomycin; trospectomycin sulfate; tyrothricin; vancomycin;vancomycin hydrochloride; virginiamycin; zorbamycin; or combinationsthereof.

The antimicrobial agent in the bone material can be an antiviral agentthat can be mixed with the bone material. Antiviral agents can include,but are not limited to, vidarabine, acyclovir, famciclovir,valacyclovir, gancyclovir, valganciclovir, nucleoside-analog reversetranscriptase inhibitors (such as AZT (zidovudine), ddI (didanosine),ddC (zalcitabine), d4T (stavudine), and 3TC (lamivudine)), nevirapine,delavirdine, protease inhibitors (such as, saquinavir, ritonavir,indinavir, and nelfinavir), ribavirin, amantadine, rimantadine,neuraminidase inhibitors (such as zanamivir and oseltamivir),pleconaril, cidofovir, foscarnet, and/or interferons.

Dispensing Apparatus

In some embodiments, there is a bone material dispensing apparatus,comprising: a tray having a proximal end, a distal end, and a bonematerial dispensing surface disposed between the proximal end and thedistal end of the tray; a foldable container configured to removablyengage the proximal end of the tray, the foldable container beingmovable in a folded configuration and an unfolded configuration about afold line in the foldable container, the foldable container having anupper compartment and a lower compartment, the lower compartment of thefoldable container configured to receive a bone material from thedispensing surface of the tray when the foldable container removablyengages the proximal end of the tray in the unfolded configuration andwhen the foldable container is in the folded configuration, the uppercompartment is configured to enclose the bone material in the lowercompartment. In some embodiments, the upper compartment and the lowercompartment can be configured to engage the tray at the same time andreceive bone material simultaneously. In some embodiments, the uppercompartment and the lower compartment can engage the tray at the sametime.

Referring to FIG. 1, it illustrates a bone material dispensing apparatus10 of the present application. The bone material dispensing apparatus 10comprises a tray 22 configured to receive a foldable container 70. Thetray 22 comprises a proximal end 36, a distal end 25 bordered by a backwall 26, a side edge 28 bordered by a side wall 30, and a bottomexterior surface 32. The tray 22 comprises a mixing surface 24 disposedbetween the proximal end 36 and the distal end 25 to mix the bonematerial and other components together (e.g., therapeutic agent,diluent, blood, cells, etc.). The mixing surface 24 can have a bowlconfiguration to allow mixing solids and liquid components of the bonematerial. Adjacent to the proximal end 36 of the tray 22 is a dispensingsurface 34 to dispense the bone material into an upper compartment 49and/or a lower compartment 48 of the foldable container 70. Thedispensing surface 34 has a length L and a width W, which allows ameasured amount of bone material to be dispensed. In the embodimentshown, the bone material is shown as granules 58. However, it will beunderstood by those of ordinary skill in the art that the bone materialcan be in other forms (e.g., a powder, paste, putty, liquid, gel, etc.).In some embodiments, the proximal end 36 of the tray 22 comprises firstchannel 38 and second channel 44. The first channel 38 of the proximalend 36 of the tray 22 is dimensioned to correspond to the uppercompartment 49 of the foldable container 70 and the second channel 44 ofthe proximal end 36 of the tray 22 is dimensioned to correspond to thelower compartment 48 of the foldable container 70 such that at least inthe unfolded configuration (shown in FIG. 2) the foldable container 70is held by the tray 22.

The first channel 38 and the upper compartment 49 could share a similargeometry such that the upper compartment 49 fits securely inside thefirst channel 38 during the filling of the bone materials. The secondchannel 44 and the lower compartment 48 could share similar geometry tofit securely inside the second channel 44 during the filling of the bonematerials. The first channel 38 and the second channel 44 can havedifferent geometry than the upper compartment 49 and the lowercompartment 48, but still be shaped to provide a sufficient constrain tothe foldable container 70 during the filling of bone materials.

The first channel 38 comprises a proximal end 40. The second channel 44comprises a distal end 46. The first channel 38 and the second channel44 have an elongated configuration to correspond to the tubularconfiguration of the foldable container 70 having longitudinal axis A. Aridge 42 of the tray 22 separates the first channel 38 and the secondchannel 44. In use, the user can slide the upper compartment 49 of thefoldable container 70 into the first channel 38 at the proximal end 40of the first channel 38 and the lower compartment 48 of the foldablecontainer 70 can slide into the second channel 44 and contact the distalend 46 of the second channel 44 so that the tray 22 holds the foldablecontainer 70 and allows filling of the foldable container 70 with bonematerial when it is in an unfolded configuration. The ridge 42 of thetray 22 is dimensioned to align with a fold line 54 of the foldablecontainer 70. Distal end 52 of the foldable container 70 can engage withthe distal end 46 of the second channel 44 and proximal end 56 of thefoldable container 70 can engage with the proximal end 40 of the firstchannel 38 when the foldable container 70 is in an unfolded or openconfiguration. Shown in FIG. 1, the foldable container 70 is in a foldedor closed configuration and upper compartment 49 of the foldablecontainer 70 contacts the lower compartment 48 of the foldable container70 where an openable seam 50 extends along longitudinal axis A. In someembodiments, the ridge 42 is separable such that the first channel 38and the second channel 44 can detach from each other, leaving only onechannel engaging the tray 22. In some embodiments, the proximal end andthe distal end of the first channel and the second channel may haveadditional constraining mechanisms such as an additional wall or bar toconstrain the foldable container 70 during loading of the material.

To mix components and/or dispense the bone material, bone materialdispensing apparatus 10, in some embodiments, comprises a spatula 12.The spatula 12 comprises a body 15 comprising a distal end 14 and ablade portion 20 comprising a blade edge 16. In some embodiments, theblade or blade edge 16 has a plurality of projections spaced a distanceapart from each other, each projection configured to engage a pluralityof ridges of the tray 22, as described herein. The spatula 12 furthercomprises a tip portion 18 to aid in dispensing the bone material intothe foldable container 70 by contact with the bone material, the mixingsurface 24 and the dispensing surface 34.

Referring to FIG. 2, it illustrates a bone material dispensing apparatus10 of the present application. The bone material dispensing apparatus 10comprises a tray 22 that has the foldable container 70 shown in anunfolded configuration. The tray 22 comprises a proximal end 36, adistal end 25 bordered by a back wall 26, a side edge 28 bordered by aside wall 30, and a bottom exterior surface 32. The tray 22 comprises amixing surface 24 disposed between the proximal end 36 and distal end 25to mix the bone material and other components together. Adjacent to theproximal end 36 of the tray 22 is a dispensing surface 34 to dispensethe bone material shown as granules 58 into the upper compartment 49and/or lower compartment 48 of the foldable container 70. The dispensingsurface 34 has a length L and a width W, which allows a measured amountof bone material to be dispensed. In the embodiment shown, the granules58 are disposed into the upper compartment 49 of the foldable container70 to partially fill the foldable container 70. The first channel 38 ofthe proximal end 36 of the tray 22 holds the upper compartment 49 of thefoldable container and the second channel 44 of the proximal end 36 ofthe tray 22 holds the lower compartment 48 of the foldable container 70in the unfolded configuration.

The first channel 38 comprises a proximal end 40. The second channel 44comprises a distal end 46. A ridge 42 of the tray 22 separates the firstchannel 38 and the second channel 44. In use, the user can slide theupper compartment 49 of the foldable container 70 into the first channel38 of the proximal end 36 of the tray 22 and the lower compartment 48 ofthe foldable container 70 can slide into the second channel 44 of theproximal end 36 of the tray so that the tray 22 holds the foldablecontainer 70 and allows filling of the foldable container 70 with bonematerial 58 when it is in an unfolded configuration. The ridge 42 of thetray 22 is dimensioned to align with fold line 54 of the foldablecontainer 70. Distal end 52 of the foldable container 70 is engaged withthe first channel 38 and proximal end 56 of the foldable container 70 isengage with the second channel 44 when the foldable container 70 is inan unfolded configuration. In some embodiments, the channels of the traymay be configured to the shape of the foldable container so as to allowease of insertion of the foldable container in the channels and allowstability of the device.

The foldable container 70, in the embodiment shown, comprises two edges,a first edge 50 a and a second edge 50 b. The first edge 50 a is on thelower compartment 48 and the second edge 50 b is on the uppercompartment 49 of the foldable container 70. Each edge has a lockingmechanism to lock the upper compartment 49 and lower compartment 48together. The locking mechanism includes slots 218 a, which are adjacentfirst edge 50 a and are spaced apart and correspond to tabs 218 b, whichare also spaced apart and adjacent second edge 50 b. To lock thefoldable container 70, first edge 50 a and second edge 50 b are broughttogether causing the foldable container 70 to fold via fold line 54, andtabs 218 b project outwardly from the exterior to engage and lock intoslots 218 a to lock the foldable container 70 in a folded configuration.In some embodiments, the locking mechanism can be alternating tabs andslots to allow locking and can include friction fitting or snapfittings. It will be understood that the locking mechanism is anoptional feature.

In some embodiments, the foldable container 70 can be made of a memoryshape polymer and/or alloy to allow the foldable container 70 to movefrom an unfolded configuration to a folded configuration without theneed for a locking mechanism. In some embodiments, a memory shapematerial may be used in the tray and/or foldable container 70, such as amemory shape polymer or alloys. Memory shape polymers include, but arenot limited to polyethers, polyacrylates, polyamides, polysiloxanes,polyurethanes, polyethers amides, polyurethane/ureas, polyether esters,polynorborene, cross-linked polymers such as cross-linked polyethyleneand cross-linked poly(cyclooctene), inorganic-organic hybrid polymers,and copolymers such as urethane/butadiene copolymers, styrene-butadienecopolymers. Memory shape alloys include, but are not limited to TiNi,CuZnAl, and FeNiAl alloys. In some embodiments, the foldable container70 and/or tray can be fabricated by injection molding of plasticmaterials comprising rigid, surgical grade plastic and/or metalmaterials.

To mix components and/or dispense the bone material, the bone materialdispensing apparatus 10, in some embodiments, comprises a spatula 12.The spatula 12 comprises a body 15 comprising a distal end 14 and ablade portion 20 comprising a blade edge 16. The spatula 12 furthercomprises a tip portion 18 to aid in dispensing the bone material intothe foldable container 70 by contact with the bone material, the mixingsurface 24 and the dispensing surface 34 of tray 22.

Referring to FIG. 3, it illustrates another embodiment of a bonematerial dispensing apparatus of the present application. The bonematerial dispensing apparatus comprises a tray 200 that has the foldablecontainer 70 shown in a folded configuration. The tray 200 comprises aproximal end 36, a distal end 25 bordered by a back wall 26. The tray200 comprises a dispensing surface 34, which can have a declineextending from the distal end 25 to the proximal end 36 of the tray 200.This allows easier movement of the bone material from the distal end 25to the proximal end 36 of the tray 200. In the embodiment shown, thedispensing surface 34 has a plurality of ridges 60 disposed on thedispensing surface 34. Each ridge has a length L and a height H. Eachridge extends longitudinally along its length between the distal end 25and the proximal end 36 of the tray 200. Each ridge has a side wall 63,which is spaced a distance apart from each other indicated by the W suchthat a measured amount of bone material can be placed between each sidewall for measured dispensing of the bone material into the foldablecontainer 70.

For example, the foldable container 70 has a diameter D and a length L′.In some embodiments, the product of length, width and height equals theproduct of π, the square of the diameter and the length of the channeldivided by 4. In other words, WDL′=πD²L′/4. Knowing this calculation, ameasured amount of the bone material can be loaded into the foldablecontainer 70 because the volume of bone material that can fit betweeneach ridge would be a predetermined amount.

In the embodiment shown in FIG. 3, the foldable container 70 is in afolded configuration via fold line 54 that can be, for example, a hingeor other rotatable fitting, that allows the upper compartment 49 and thelower compartment 48 of the foldable container 70 to be folded andpartially enclose the bone material. The foldable container 70 has anopening at the distal end 52 and an opening at the proximal end 56.These openings, in some embodiments, can be configured to receive aplunger and the plunger would extend along longitudinal axis A.

Referring to FIG. 4, it illustrates another embodiment of the tray 300that is configured to receive a foldable container (not shown). The tray300 comprises a back wall 26 that can have a declining surface extendingfrom the distal end 25 of the tray. The tray comprises a dispensingsurface 34, which can also have a declining surface extending fromdistal end 25 to the proximal end 36 of the tray 300. This decliningsurface can be from about 2 degrees, 3 degrees, 4 degrees, 5 degrees toabout 6 degrees. In the embodiment shown, the dispensing surface 34 hasa plurality of ridges 60 disposed on the dispensing surface 34. Eachridge has a length L and a height H. Each ridge extends longitudinallyalong its length between the distal end 25 to the proximal end 36 of thetray 300. Each ridge has a side wall 63, which is spaced a distanceapart from each other indicated by the W such that a measured amount ofbone material can be placed between each side wall for measureddispensing of the bone material into the foldable container. There aremultiple ridges and multiple widths (W, W₁, W₂ . . . W_(n)). The firstchannel at the proximal end 36 has a diameter D and a length L′. Theproduct of length, the sum of all widths and heights equal the productof π, the square of the diameter and the length of the channel dividedby 4. In other words, L(W+W₁+W₂ . . . W_(n))H=πD²L′/4. Thus, the usercan place the bone material between one or more ridges and those ridgeswill be configured to have a predetermined amount of bone material to bedisposed between them. In this way, a measured amount of bone materialcan be dispensed from the tray 300. In some embodiments, there can be anindex marker (not shown) disposed between ridges to provide a visualindicator to a user of the amount of bone material and/or therapeuticagent (e.g., 5 g, 6 g, 7 g, etc.) that can be disposed between theplurality of ridges 60 to be dispensed.

In some embodiments, the foldable container and/or the tray compriseadditional measuring structures such as multiple channels and/or ridgesto segregate the granules 58 into defined, smaller quantities. Theseadditional measuring structures can further aid in spreading thegranules 58 evenly along the axis of the foldable container 70 andprevent packing of the granules 58 too tightly, thus facilitating easierintroduction of the granules 58 out of the foldable container 70 andinto a device or targeted location.

Referring to FIG. 5, it illustrates another embodiment of a bonematerial dispensing apparatus of the present application. The bonematerial dispensing apparatus comprises a tray 400 that has the foldablecontainer 70 in an unfolded configuration. The tray 400 comprises aproximal end 36, a distal end 25 bordered by a back wall 26. The tray400 comprises a dispensing surface 34 extending from the distal end 25to the proximal end 36 of the tray 400 and a mixing surface 24 shown asa bowl configuration to allow mixing of the bone material. In theembodiment shown, the dispensing surface 34 has a plurality of ridges 60disposed on the dispensing surface 34. Each ridge has a length L and aheight H. Each ridge extends longitudinally along its length between thedistal end 25 and the proximal end 36 of the tray 400. Each ridge has aside wall 63, which is spaced a distance apart from each other indicatedby the W₁ or W₂, such that a measured amount of bone material can beplaced between each side wall for measured dispensing of the bonematerial into the foldable container 70. In the embodiment shown, thereare multiple ridges and multiple widths (W₁, W₂ . . . W_(n)). Thefoldable container 70 having distal end 52 and proximal end 56 is shownin an unfolded configuration and the foldable container 70 has adiameter D and a length L′. The product of length, the sum of all widthsand heights equals the product of π, the square of the diameter and thelength of the channel divided by 4. In other words, L(W₁+W₂ . . .W_(n))H=πD²L′/4. Thus, the user can place the bone material between oneor more ridges and those ridges will be configured to have apredetermined amount of bone material to be disposed between them. Inthis way, a measured amount of bone material can be dispensed from thetray. It will be understood that in some embodiments, the plurality ofridges 60 may have different lengths and widths and appear as differentpatterns on the dispensing surface 34 of the tray 400.

The foldable container 70, in the embodiment shown, comprises two edges,a first edge 50 a and a second edge 50 b. The first edge 50 a is on thelower compartment 48 and the second edge 50 b is on the uppercompartment 49 of the foldable container 70. The edges have a lockingmechanism to lock the upper compartment 49 and lower compartment 48together. The locking mechanism includes slots 218 a, which are adjacentfirst edge 50 a and are spaced apart and correspond to tabs 218 b, whichare also spaced apart and adjacent second edge 50 b. To lock thefoldable container 70, first edge 50 a and second edge 50 b are broughttogether causing the foldable container 70 to fold via fold line 54 andtabs 218 b project outwardly from the exterior to engage and lock intoslots 218 a to lock the foldable container 70 in a folded configuration.In some embodiments, there is a locking mechanism such as snap-fit ortab-slot fitting to removable engage the tray 400 and the foldablecontainer 70 such that the tray 400 and the foldable container 70 can beremovably attached to the tray 400 and provide stability during thedispensing process. In the embodiment shown in FIG. 5, the foldablecontainer 70 engages the tray 400 by its tabs 218 b and there are nochannels to hold the tray in the desired position.

Referring to FIG. 6, it illustrates another embodiment of a bonematerial dispensing apparatus of the present application. The bonematerial dispensing apparatus comprises a tray 500 that has the foldablecontainer 70 shown in a folded configuration. The tray 500 comprises aproximal end 36, a distal end 25 bordered by a back wall 26. The tray500 comprises a dispensing surface 34 extending from the distal end 25to the proximal end 36 of the tray 500 and a mixing surface 24 shown asa bowl configuration to allow mixing of the bone material. In theembodiment shown, the dispensing surface 34 has a plurality of ridges 60disposed on the dispensing surface 34. Each ridge has a side wall 63,which is spaced a distance apart from each other such that a measuredamount of bone material shown as granules 58 is placed between each sidewall for measured dispensing of the bone material into the foldablecontainer 70.

In the embodiment shown in FIG. 6, the foldable container 70 has adiameter D and a length L′ and is shown in a folded configuration viafold line 54 that can be, for example, a hinge or other rotatablefitting, that allows upper compartment 49 and lower compartment 48 ofthe foldable container 70 to be folded and partially enclose the bonematerial 58. Foldable container 70 has an opening at the distal end 52and an opening at the proximal end 56. These openings, in someembodiments, can be configured to receive a plunger and the plungerwould extend along longitudinal axis A. In some embodiments, seam 50extends longitudinally along axis A and there may be a lockingmechanism, which locks the foldable container 70 along the longitudinalaxis A. In some embodiments, the foldable container 70 is removablyattached to the tray 500 by an attachment member 55. The attachmentmember 55 extends parallel or substantially parallel to the foldablecontainer 70 and holds the foldable container 70 in place withoutlocking the foldable container 70 completely. This allows easyattachment, filling and removal of the foldable container 70 from thetray 500.

Referring to FIG. 7, it illustrates a perspective view of the foldablecontainer 70 in the unfolded configuration (shown in the upper panel)and the folded configuration (shown in the lower panel). In theembodiment shown, the foldable container 70 comprises openable seam 50that separates into two edges, a first edge 50 a and a second edge 50 b.The first edge 50 a is on the lower compartment 48 and the second edge50 b is on the upper compartment 49 of the foldable container 70. Theedges have a locking mechanism to lock the upper compartment 49 andlower compartment 48 together. The locking mechanism includes slots 218a, which are adjacent first edge 50 a and are spaced apart andcorrespond to tabs 218 b, which are also spaced apart and adjacentsecond edge 50 b. To lock the foldable container 70, first edge 50 a andsecond edge 50 b are brought together causing the foldable container 70to fold via fold line 54 and tabs 218 b project outwardly from theexterior to engage and lock into slots 218 a to lock the foldablecontainer 70 in a folded configuration. In some embodiments, slots 218 aor tabs 218 b can correspond to slots and/or tabs on the tray (notshown) to allow the foldable container 70 to removably attach to thetray and provide stability during the dispensing process. In theembodiment shown in FIG. 7, there is an opening at the distal end 52 ofthe foldable container 70 and an opening at the proximal end 56 of thecontainer 70. These openings, in some embodiments, can be configured toreceive a plunger and the plunger would extend along longitudinal axisA.

Referring to FIG. 8, it illustrates a perspective view of the foldablecontainer 70 in a folded configuration via fold line 54 that can be, forexample, a hinge or other rotatable fitting, that allows the uppercompartment 49 and the lower compartment 48 of the foldable container 70to be folded and partially enclose the bone material shown as granules58. The foldable container 70 has an opening at the distal end 52 and anopening at the proximal end 56. These openings, in some embodiments, canbe configured to receive a plunger.

In some embodiments, the foldable container 70 is configured to beloaded with the bone material 58 and inserted into an insertion device80, such as for example, a cannula, a needle or a sleeve to allowdelivery of the bone material 58 to the target tissue site. The cannula,needle or sleeve is designed to cause minimal physical and psychologicaltrauma to the patient. Cannulas, needles, or sleeves include tubes thatmay be made from materials, such as for example, polyurethane, polyurea,polyether(amide), PEBA, thermoplastic elastomeric olefin, copolyester,and styrenic thermoplastic elastomer, steel, aluminum, stainless steel,titanium, nitinol, metal alloys with high non-ferrous metal content anda low relative proportion of iron, carbon fiber, glass fiber, plastics,ceramics or combinations thereof. The cannula, needle or sleeve mayoptionally include one or more tapered regions. In various embodiments,the cannula, needle or sleeve may be blunt, beveled, diamond point, balltip, trocar tip, etc. The cannula, needle or sleeve may also have a tipstyle vital for accurate treatment of the patient depending on the bonedefect. Examples of tip styles include, for example, Trephine, Cournand,Veress, Huber, Seldinger, Chiba, Francine, Bias, Crawford, deflectedtips, Hustead, Lancet, or Tuohey. In various embodiments, the cannula,needle or sleeve may also be non-coring and have a sheath covering it toavoid unwanted needle sticks.

In some embodiments, the shape of the tray and the foldable containermay be selected for particular applications. Such shape andconfiguration may include, for example, the basic shape of the tray(e.g., a square shaped box, etc.) and the foldable container (e.g., atubular shaped container).

Referring to FIG. 9, it illustrates a perspective view of the foldablecontainer 70 in a folded configuration via fold line 54 that can be, forexample, a hinge or other rotatable fitting, that allows the uppercompartment 49 and the lower compartment 48 of the foldable container 70to be folded and partially enclose the bone material shown as granules58. The foldable container 70 has an opening at the distal end 52 and anopening at the proximal end 56. These openings, in some embodiments, canbe configured to receive a plunger. In the embodiment shown, proximalend 56 has a tapered end and when it is slid into a sleeve 90, thefoldable container 70 conforms to the sleeve 90 and is locked andclosed, whereby inserting a plunger into the proximal end 56 of thefoldable container 70, the bone material 58 can be delivered to the bonedefect. In some embodiments, the tapered end has a slant opening with anangle from about 0.1 to about 90 degree measuring from the longitudinalaxis of the foldable container. Preferably, the slant opening has anangle of about 45 degree. The slant opening ease the insertion of thefoldable container into other device with less resistance as the initialcontact surface between the foldable container and the other devicedecreases.

Referring to FIG. 10, it illustrates a perspective view of the foldablecontainer 70 in a folded configuration via fold line 54 that can be, forexample, a hinge or other rotatable fitting, that allows the uppercompartment 49 and the lower compartment 48 of the foldable container 70to be folded and partially enclose the bone material. The foldablecontainer 70 has seam 50 and there is an opening at the distal end 52and an opening at the proximal end 56 of the foldable container 70.These openings, in some embodiments, can be configured to receive aplunger. In the embodiment shown, proximal end 56 and distal end 52 havea tapered configuration. The distal end 52 has and angled tip 92 forease of insertion into sleeve 90. The foldable container 70 comprisestabs 94 disposed at opposite surfaces of the foldable container 70,which allow the foldable container 70 to be locked and closed in sleeve90. In some embodiments, the tapered end has a slant opening with anangle from about 0.1 to about 90 degree measuring from the longitudinalaxis of the foldable container. Preferably, the slant opening has anangle of about 45 degree. The slant opening ease the insertion of thefoldable container into other device with less resistance as the initialcontact surface between the foldable container and the other devicedecreases.

FIG. 11 illustrates another aspect of the bone material dispensingapparatus 10 comprising spatula 12 and a tray having the first channel38 and the second channel 44 that are configured to receive a foldablecontainer 100. The foldable container 100 comprises an upper compartment102, a lower compartment 104, a fold line 108, an openable seam 114 anda needle 106. The bone material dispensing apparatus 10 furthercomprises a plunger 110 and a tip cap 112. The plunger 110 allowsdelivery of the bone material from the bone material dispensingapparatus 10 by sliding the plunger 110 through the loaded foldablecontainer 100 to deliver the bone material out the needle 106 and to thebone defect. In some embodiments, the plunger 110 generally has asmaller diameter compared to the foldable container 100. In someembodiments, the plunger 110 comprises an elongated portion that extendsat least the same length as the length of the foldable container 100.The foldable container 100 can be filled with bone material by placingthe foldable container in the tray and mixing bone material in mixingsurface 24 of the tray and loading the foldable container 100 with bonematerial when the foldable container 100 is loaded in first channel 38and second channel 44 of the tray. The foldable container 100 is thenassembled with the needle 106 and plunger 110, and the bone material canbe delivered to the patient with ease and reduction in clogging of thefoldable container 100.

FIG. 12 illustrates a tip 230 of the foldable container. In someembodiments, the tip 230 comprises various shapes including, but notlimited to, an H shape 202, clover shape 204, square shape 206,rectangle shape 208, oval shape 210, and circle shape 212. In someembodiments, the tip comprises additional shapes. FIG. 12 furtherillustrates locking mechanism 220. In some embodiments, the lockingmechanism comprises a snap fit fitting 214, a friction fit fitting 216and a tab-slot fitting 218. In some embodiments, this tip geometry isconsistent for the entire length of the folded configuration. In someembodiments, the locking mechanism could include a third and/or a fourthfolding element that are connected to the upper and/or lowercompartments by additional fold lines. These additional folding elementswould enable the user to fold over and secure closed the foldablecontainer. FIG. 14 illustrates a container 120 with a third foldingelement. In this configuration, the container comprises an uppercompartment 49, a lower compartment 48, and a third ½ tube 122. Theupper compartment is joined to the lower compartment by a fold line 54.A third ½ tube of slightly larger diameter is joined to the lowercompartment by a second fold line 124. In the closed configuration, theupper and lower compartments are loaded with bone material and foldedtogether to create a circular tube. The slightly larger third ½ tubeattached to the lower compartment via the second fold line is closedover top of the upper container to lock the folded container closed.

FIG. 13 illustrates different spatulas 12, where the body issubstantially rectangular or round. The spatula may comprise a tipportion 18 that is configured for grinding and/or mixing bone materials.The spatula may have a distal portion 14 that is configured for grindingand mixing materials. In some embodiments, the blade portion 20 of thespatula comprises various shapes corresponding to the shapes of theridges and the space between the ridges of the tray. The blade portionmay include a rectangular cutout 302 corresponding to a rectangularridge of the tray, a triangular cutout 304 corresponding to a triangularridge of the tray, or an arcuate/circular cutout 306 corresponding to anarcuate/circular ridge of the tray. In some embodiments, the number ofcutouts may be less than the number of ridges.

In various embodiments, a kit is provided comprising the bone materialdispensing apparatus, which includes the tray and the foldablecontainer. The kit may include additional parts along with the bonematerial dispensing apparatus including the bone material and othercomponents to be used to administer the bone material (e.g., wipes,needles, syringes, other mixing devices, etc.). The kit may include thebone material in a first compartment. The second compartment may includea vial holding the carrier and any other instruments needed for thedelivery. A third compartment may include gloves, drapes, wounddressings and other procedural supplies for maintaining sterility of theimplanting process, as well as an instruction booklet, which may includea chart that shows how to administer the bone material after mixing it.A fourth compartment may include additional needles and/or sutures. Eachtool may be separately packaged in a plastic pouch that is sterilized. Afifth compartment may include an agent for radiographic imaging. A coverof the kit may include illustrations of the implanting procedure and aclear plastic cover may be placed over the compartments to maintainsterility.

In various embodiments, one or more components of the bone materialdispensing apparatus is sterilized by radiation in a terminalsterilization step in the final packaging. Terminal sterilization of aproduct provides greater assurance of sterility than from processes suchas an aseptic process, which require individual product components to besterilized separately and the final package assembled in a sterileenvironment.

In various embodiments, gamma radiation is used in the terminalsterilization step, which involves utilizing ionizing energy from gammarays that penetrates deeply into the bone material dispensing apparatus.Gamma rays are highly effective in killing microorganisms, they leave noresidues, nor do they have sufficient energy to impart radioactivity tothe apparatus. Gamma rays can be employed when the apparatus is in thepackage and gamma sterilization does not require high pressures orvacuum conditions, thus, package seals and other components are notstressed. In addition, gamma radiation eliminates the need for permeablepackaging materials.

In various embodiments, electron beam (e-beam) radiation may be used tosterilize one or more components of the bone material dispensingapparatus. E-beam radiation comprises a form of ionizing energy, whichis generally characterized by low penetration and high-dose rates.E-beam irradiation is similar to gamma processing in that it altersvarious chemical and molecular bonds on contact, including thereproductive cells of microorganisms. Beams produced for e-beamsterilization are concentrated, highly-charged streams of electronsgenerated by the acceleration and conversion of electricity.

Other methods may also be used to sterilize the dispensing apparatusincluding, but not limited to, gas sterilization such as, for example,with ethylene oxide or steam sterilization.

Methods of Use

A method of filling bone material into a foldable container is provided.The method comprises: placing a bone material in or on a dispensingsurface of a tray, the tray having a proximal end, a distal end, and thedispensing surface disposed between the proximal end and the distal endof the tray; transferring the bone material from the dispensing surfaceof the tray to fill a foldable container with the bone material, thefoldable container configured to removably engage the proximal end ofthe tray, the foldable container being movable in a folded configurationand an unfolded configuration about a fold line in the foldablecontainer, the foldable container having an upper compartment and alower compartment, the lower compartment of the foldable containerconfigured to receive the bone material from the dispensing surface ofthe tray when the foldable container removably engages the proximal endof the tray in the unfolded configuration; and folding the uppercompartment on the lower compartment of the foldable container toenclose the bone material in the foldable container when the foldablecontainer is in the folded configuration thereby filling the foldablecontainer with bone material.

The bone material can be mixed with liquid material and optionally atherapeutic agent using the spatula, the mixing surface and thedispensing surface of the tray until the desired consistency of the bonematerial is achieved (e.g., putty, paste, etc.). The bone material canbe mixed with a suitable diluent and then loaded into the foldablecontainer. The foldable container may have enough space to allow for thebone material and a volume of diluent to be mixed. In some embodiments,the diluent includes dextrose, other sugars including but not limited tosucrose, fructose, glucose, lactated ringer's, polyols including but notlimited to mannitol, xylitol, sorbitol, maltitol, lactitol,polysaccharides including but not limited to native or pre-gelatinizedstarch, maltodextrins, cyclodextrins, mineral compounds including butnot limited to dicalcium or tricalcium phosphate, either dihydrate oranhydrous, cellulose derivatives including but not limited tomicrocrystalline cellulose, lactoses either monohydrates thereof oranhydrous, as well as their mixtures such as dicalcium phosphatedihydrate, mannitol, pre-gelatinized maize starch, microcrystallinecellulose and their mixtures, water and/or NaCl (saline). In someembodiments, the saline is 0.90% saline or 0.45% saline. In someembodiments, other delivery vehicles can be used for example, D5W(dextrose in 5% water), D5NS (dextrose in 5% water and normal saline)and D5W/½NS (D5W and ½ normal saline), blood, mesenchymal stem cells, orthe like.

In some embodiments, the method further comprises removing the filledfoldable container from the tray, placing a plunger in the filledfoldable container at a proximal opening of the foldable container;placing a needle at a distal opening of the foldable container;inserting the needle at a bone defect; and delivering the bone materialfrom the foldable container to the bone defect. In some embodiments, themethod further comprises removing the filled foldable container from thetray; placing the filled foldable container in a delivery cannula;placing a plunger in the filled foldable container at a proximal openingof the foldable container; inserting the delivery cannula at a bonedefect; and delivering the bone material in the foldable container tothe bone defect.

In some embodiments, the foldable container in an open and unfoldedconfiguration can be rotated horizontally such that the uppercompartment and the lower compartment may switch their correspondingpositions with the first channel and the second channel. After the uppercompartment on the first channel is filled with the bone material, itcan be rotated such that the lower compartment will be disposed on thefirst channel to receive bone materials. In some embodiments, thefoldable container in an open and unfolded configuration can be rotated90 degrees such that the longitudinal axis of the foldable container isperpendicular to the axis formed between proximal end 36 and distal end25 of the tray. In some embodiments, the longitudinal axis of thefoldable container is parallel to a longitudinal axis of the ridge ofthe tray.

The bone material dispensing apparatus can be used to treat a variety ofconditions including osteoporosis, bone fracture repair or healing,dental procedures for which increased bone formation in the jaw is ofclinical benefit, repair of craniofacial bone defects induced by traumaor congenital defects such as cleft palate/lip, and a number of othermusculoskeletal disorders where native bone growth is inadequate, whichwill be evident to those of ordinary skill in the art. The bone materialcan be administered to treat open fractures and fractures at high riskof non-union, and in subjects with spinal disorders, including subjectsin need of spine fusion (e.g., anterior lumbar interbody fusion,posterior lumbar spinal fusion, and cervical spine fusion) or subjectshaving degenerative disc disease or arthritis affecting the lumbar andcervical spine.

Although the invention has been described with reference to embodiments,persons skilled in the art will recognize that changes may be made inform and detail without departing from the spirit and scope of thedisclosure.

What is claimed is:
 1. A bone material dispensing apparatus, comprising:a tray having a proximal end, a distal end, a bone material dispensingsurface disposed between the proximal end and the distal end of the trayand a container holding surface disposed at the proximal end of the trayadjacent to the bone material dispensing surface; a foldable containerconfigured to removably engage the proximal end of the tray, thefoldable container being movable in a folded configuration and anunfolded configuration about a fold line in the foldable container, thefoldable container having an upper compartment and a lower compartment,the lower compartment of the foldable container configured to receive abone material from the dispensing surface of the tray when the foldablecontainer removably engages the proximal end of the tray in the unfoldedconfiguration and when the foldable container is in the foldedconfiguration, the upper compartment is configured to enclose the bonematerial in the lower compartment, wherein the proximal end and thedistal end of the tray define a longitudinal axis, and the longitudinalaxis of the tray is perpendicular to a longitudinal axis of the foldablecontainer formed by a proximal end and a distal end of the foldablecontainer when the foldable container engages the proximal end of thetray; and wherein the container holding surface comprises a firstchannel and a second channel configured to hold the upper compartmentand the lower compartment of the foldable container.
 2. The bonematerial dispensing apparatus of claim 1, wherein the first channel ofthe proximal end of the tray is dimensioned to correspond to the uppercompartment of the foldable container and the second channel of theproximal end of the tray is dimensioned to correspond to the lowercompartment of the foldable container such that at least in the unfoldedconfiguration the foldable container is held by the tray.
 3. The bonematerial dispensing apparatus of claim 1, wherein the foldable containerhas a tubular shaped configuration and a proximal opening configured toreceive a plunger and a distal opening configured to receive a cannulaor fit within a cannula.
 4. The bone material dispensing apparatus ofclaim 1, wherein the dispensing surface comprises a mixing surfacecomprising a bowl configured to mix the bone material.
 5. The bonematerial dispensing apparatus of claim 1, wherein the dispensing surfacecomprises a decline extending from the distal end of the tray to theproximal end of the tray.
 6. The bone material dispensing apparatus ofclaim 1, wherein the dispensing surface comprises a plurality of ridgesextending from the distal end to a region adjacent the proximal end,each of the plurality of ridges having a side wall and each of theplurality of ridges spaced a distance apart from each other such that ameasured amount of bone material can be placed between each side wall ofat least two of the plurality of ridges for measured dispensing of thebone material into the foldable container.
 7. The bone materialdispensing apparatus of claim 6, the apparatus further comprising aspatula having a blade, the blade having a plurality of projectionsspaced a distance apart from each other, each projection configured tofit between each side wall of the plurality of ridges so as to allowmeasured dispensing of the bone material.
 8. The bone materialdispensing apparatus of claim 1, wherein the fold line comprises a hingethat rotably connects the upper compartment and the lower compartment ofthe foldable container in the unfolded configuration.
 9. The bonematerial dispensing apparatus of claim 1, wherein the foldable containerhas a locking mechanism comprising a snap fit fitting, or a projectionoutwardly extending from an exterior of the foldable container.
 10. Thebone material dispensing apparatus of claim 1, wherein the foldablecontainer comprises a shape memory polymer.
 11. The bone materialdispensing apparatus of claim 1, wherein (i) the foldable container hasa tubular shape and is configured to receive a plunger at a proximalopening of the foldable container and a needle at a distal opening ofthe foldable container; or (ii) the foldable container is configured tobe inserted into a cannula.
 12. The bone material dispensing apparatusof claim 1, wherein the proximal end of the foldable container isconfigured to receive a plunger, and the foldable container has anexterior having tapering extending from a region of the foldablecontainer to the distal end of the foldable container.
 13. The bonematerial dispensing apparatus of claim 1, wherein the foldable containerhas a round, oval, rectangular, square, clover or an irregular shapedtip.